Jiayu Liu, Qiunan Zhou, Kai Meng, Xiaojuan Yang, Bin Ma, Chunxia Su, Xiangguo Duan
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Aspirin may suppress the expression of TIGIT on T cells and Regulatory T cells (Tregs) and inhibit T cell viability, and therefore induce tumor cell apoptosis. TIGIT is expressed at higher levels on infiltrating lymphocytes within CRC tumor tissue than adjacent. Further, aspirin could inhibit Jurkat cell proliferation and induce apoptosis via downregulation of TIGIT expression and the anti-apoptosis B cell lymphoma 2 (BCL2) protein and upregulation of BCL2-associated X protein (BAX) expression. 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引用次数: 0
摘要
T细胞免疫球蛋白和ITAM结构域(TIGIT)是最近发现的一种协同共抑制分子,在癌症的免疫反应和肿瘤免疫逃逸中发挥着重要作用。重要的是,CD155 是 TIGIT 的受体,CD155 通过与共刺激免疫受体 CD226(DNAM-1)以及抑制性检查点受体 TIGIT 和 CD96 的相互作用向免疫细胞传递信号。阿司匹林(ASA)已被证明能降低结直肠癌(CRC)细胞的生长和存活率,但其中涉及的免疫学机制尚未得到充分阐明。本研究调查了阿司匹林对小鼠 CRC 和 Jurkat 细胞的影响。阿司匹林可抑制 T 细胞和调节性 T 细胞(Tregs)上 TIGIT 的表达,抑制 T 细胞的活力,从而诱导肿瘤细胞凋亡。TIGIT 在 CRC 肿瘤组织内浸润淋巴细胞上的表达水平高于邻近淋巴细胞。此外,阿司匹林可通过下调 TIGIT 和抗凋亡 B 细胞淋巴瘤 2(BCL2)蛋白的表达以及上调 BCL2 相关 X 蛋白(BAX)的表达,抑制 Jurkat 细胞增殖并诱导细胞凋亡。本研究表明,阿司匹林可通过 TIGIT-BCL2-BAX 信号通路减少白细胞介素-10 和转化生长因子-β1 的分泌,从而抑制 T 细胞功能的特定方面,从而改善效应 T 细胞的功能,抑制肿瘤的进展。
Aspirin Inhibits Colorectal Cancer via the TIGIT-BCL2-BAX pathway in T Cells.
The T cell immunoglobulin and ITAM domain (TIGIT) is a recently discovered synergistic co-suppressor molecule that plays an important role in immune response and tumor immune escape in the context of cancer. Importantly, CD155 acts as a receptor for TIGIT, and CD155 signaling to immune cells is mediated through interactions with the co-stimulatory immune receptor CD226 (DNAM-1) and the inhibitory checkpoint receptors TIGIT and CD96. Aspirin (ASA) has been shown to reduce the growth and survival of colorectal cancer (CRC) cells, but the immunological mechanisms involved have not been sufficiently elucidated. In the present study the effects of aspirin on CRC in mice and on Jurkat cells were investigated. Aspirin may suppress the expression of TIGIT on T cells and Regulatory T cells (Tregs) and inhibit T cell viability, and therefore induce tumor cell apoptosis. TIGIT is expressed at higher levels on infiltrating lymphocytes within CRC tumor tissue than adjacent. Further, aspirin could inhibit Jurkat cell proliferation and induce apoptosis via downregulation of TIGIT expression and the anti-apoptosis B cell lymphoma 2 (BCL2) protein and upregulation of BCL2-associated X protein (BAX) expression. The present study suggests that aspirin can inhibit specific aspects of T cell function by reducing interleukin-10 and transforming growth factor-β1 secretion via the TIGIT-BCL2-BAX signaling pathway, resulting in improved effector T cell function that inhibits tumor progression.
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